Gamma-aminobutyric Acid Concentrations Research Articles

MR-Spectroscopy and Survival in Mice with High Grade Glioma Undergoing Unrestricted Ketogenic Diet

Glioblastoma multiforme (GBM) is considered the most malignant form of primary brain tumor. Despite multimodal treatment, prognosis remains poor. Ketogenic diet (KD) has been suggested for the treatment of GBM. In this study, the syngenic, orthotopic GL261 mouse glioma model was used to evaluate the effects of KD on the metabolic responses of the tumor using 7T magnetic resonance imaging/spectroscopy. GL261 cells were injected into the caudate nucleus of mice. Following implantation, animals were fed with standard chow or underwent a KD. 18 days after initiating the diet, mice fed with KD displayed significantly higher plasmatic levels of ketone bodies and survived longer than those fed with the standard diet. Decreased concentrations of gamma-aminobutyric acid, N-Acetyl-Aspartate and N-acetylaspartylglutamate were found in tumor tissue after 9 days into the KD, while a huge increase in beta-hydroxybutyrate (bHB) was detected in tumor tissue as compared to normal brain. The accumulation of bHB in the tumor tissue in mice undergoing the KD, may suggest either elevated uptake/release of bHB by tumor cells, or the inability of tumor cells in this context to use it for mitochondrial metabolism.

A Computational Model to Investigate GABA-Activated Astrocyte Modulation of Neuronal Excitation.

Gamma-aminobutyric acid (GABA) is critical for proper neural network function and can activate astrocytes to induce neuronal excitability; however, the mechanism by which astrocytes transform inhibitory signaling to excitatory enhancement remains unclear. Computational modeling can be a powerful tool to provide further understanding of how GABA-activated astrocytes modulate neuronal excitation. In the present study, we implemented a biophysical neuronal network model to investigate the effects of astrocytes on excitatory pre- and postsynaptic terminals following exposure to increasing concentrations of external GABA. The model completely describes the effects of GABA on astrocytes and excitatory presynaptic terminals within the framework of glutamatergic gliotransmission according to neurophysiological findings. Utilizing this model, our results show that astrocytes can rapidly respond to incoming GABA by inducing Ca2+ oscillations and subsequent gliotransmitter glutamate release. Elevation in GABA concentrations not only naturally decreases neuronal spikes but also enhances astrocytic glutamate release, which leads to an increase in astrocyte-mediated presynaptic release and postsynaptic slow inward currents. Neuronal excitation induced by GABA-activated astrocytes partly counteracts the inhibitory effect of GABA. Overall, the model helps to increase knowledge regarding the involvement of astrocytes in neuronal regulation using simulated bath perfusion of GABA, which may be useful for exploring the effects of GABA-type antiepileptic drugs.

Neurotoxic effects of lactational exposure to perfluorooctane sulfonate on learning and memory in adult male mouse

The present study aims to examine the effect of early lactational perfluorooctane sulfonate (PFOS) exposures on learning and memory in male mice and reveal the underlying mechanisms involved. PFOS solution was orally administered to dams from the postpartum days 1–14, so that pups would be exposed through breast milk. At 8–10 weeks of age, we performed object location test (OLT), object recognition test (ORT), and pairwise visual discrimination (VD) task. We also performed in vivo microdialysis, and mRNA and protein analysis of genes responsible for hippocampal development and function. In both OLT and ORT, the performance of mice in the PFOS-exposed group was significantly lower than those in the control group. In the VD task, the PFOS-exposed group learned significantly slower than the control group. Concentrations of glutamate and gamma-aminobutyric acid in the dorsal hippocampus were significantly higher in the PFOS-exposed group than in the control group. No notable differences were shown in our mRNA and protein studies. The present study showed that lactational PFOS exposure has a profound, long-lasting neurotoxic effect in the hippocampus and consequently leads to learning and memory deficits.

GABA concentrations in the anterior cingulate and dorsolateral prefrontal cortices: Associations with chronic cigarette smoking, neurocognition, and decision making.

Chronic cigarette smoking is associated with regional metabolite abnormalities in choline-containing compounds, creatine-containing compounds, glutamate, and N-acetylaspartate. The effects of cigarette smoking on anterior frontal cortical gamma-aminobutyric acid (GABA) concentration are unknown. This study compared chronic smokers (n = 33) and nonsmokers (n = 31) on anterior cingulate cortex (ACC) and right dorsolateral prefrontal cortex (DLPFC) GABA+ (the sum of GABA and coedited macromolecules) concentrations and associations of GABA+ levels in these regions with seven neurocognitive domains of functioning, decision making, and impulsivity measures. Smokers had significantly lower right DLPFC GABA+ concentration than nonsmokers, but groups were equivalent on ACC GABA+ level. Across groups, greater number of days since end of menstrual cycle was related to higher GABA+ level in the ACC but not right DLPFC GABA+ concentration. In exploratory correlation analyses, higher ACC and right DLPFC GABA+ levels were associated with faster processing speed and better auditory-verbal memory, respectively, in the combined group of smokers and nonsmokers; in smokers only, higher ACC GABA+ was related to better decision making and auditory-verbal learning. This study contributes additional novel data on the adverse effects of chronic cigarette smoking on the adult human brain and demonstrated ACC and DLPFC GABA+ concentrations were associated with neurocognition and decision making/impulsivity in active cigarette smokers. Longitudinal studies on the effects of smoking cessation on regional brain GABA levels, with a greater number of female participants, are required to determine if the observed metabolite abnormalities are persistent or normalize with smoking cessation.

Crosstalk between GABA and ALA to improve antioxidation and cell expansion of tomato seedling under cold stress

Cold stress inhibits plant growth and ultimately affects yield formation. Exogenous 5- aminolevulinic acid (ALA) can improve tomato cold tolerance and promote plant growth. It significantly up-regulated glutamate decarboxylase gene (SlGAD4) expression, which was involved in gamma-aminobutyric acid (GABA) synthesis. Whether the GABA was involved in ALA-regulated tomato cold tolerance and plant growth was unclear. Thus, this study aimed to explore the effects of exogenous ALA and GABA on endogenous ALA and GABA synthesis. The roles of ALA and GABA on regulating the antioxidation and cell morphological changes related to plant growth in tomato leaves were further explored. And the internal relationship between ALA and GABA in increasing tomato cold tolerance was also determined. Results showed that cold stress increased the glutamate (Glu) and GABA contents and reduced the ALA content. The exogenous ALA- or GABA-treated plants demonstrated decreased Glu content and increased GABA or ALA contents. Exogenous ALA or GABA treatment promoted the expansion of upper epidermal (UEP) and palisade parenchymal (PA) cells and up-regulated the xyloglucan endotransglucosylase/hydrolases gene (SlXTH23) expression in tomato leaves. Exogenous ALA or GABA significantly alleviated cold-induced tomato membrane lipid peroxidation and enhanced C-repeat binding factors gene (SlCBF2) expression and superoxide dismutase (SOD), catalase (CAT), APX and GR activities. Inhibiting endogenous GABA with 3-mercaptopropionic (3-mp) dramatically decreased the size of UEP and PA cells and reduced SOD and CAT activities. It also aggravated the membrane peroxidation damage, which notably weakened the alleviated effects of exogenous ALA. Inhibiting endogenous ALA with gabaculine (gaba) partly inhibited the alleviated effects of exogenous GABA. These findings indicated that spray with exogenous ALA or GABA could increase endogenous ALA and GABA levels in tomato leaves. In addition, endogenous GABA and ALA could be mutually converted through Glu. Exogenous ALA and GABA promoted cell expansion, stimulated the antioxidant system and might enhance tomato cold tolerance via endogenous GABA signal and the C-repeat binding factor regulation pathway, thereby alleviating cold inhibited plant growth. In conclusion, GABA crosstalk with ALA improved tomato cold stress tolerance and promoted plant growth by regulating antioxidants and cell expansion.

Application of high-GABA producing Lactobacillus plantarum isolated from traditional cabbage pickle in the production of functional fermented whey-based formulate

In this study, a fermented whey-based formulate with enhanced levels of gamma aminobutyric acid (GABA) was produced by using a selected lactic acid bacteria isolated from traditional cabbage pickle. 16S rRNA gene sequencing resulted in identification of high GABA-producing isolate as Lactobacillus plantarum which was used as single or co-culture with Lactococcus lactis subsp. lactis (a proteolytic strain from the microbial bank). The isolated L. plantarum showed higher proteolytic, acidification and GABA-producing activity in cheese whey compared to Lc. lactis Subsp. lactis. However, the highest concentration of GABA (365.6 mg/100 mL) was found in the samples fermented using co-cultures of these strains. Moreover, addition of soy protein hydrolysate (SPH) to whey resulted in a significant enhancement in GABA concentration in the final product upon fermentation. Moreover, in the co-cultured sample containing higher amount of SPH, the lower fermentation time was observed. The results of this study showed that L. plantarum isolated from cabbage pickle is a good candidate to be used as p starter culture to manufacture a novel functional whey formulate enriched with GABA.

Effects of bifrontal transcranial direct current stimulation on brain glutamate levels and resting state connectivity: multimodal MRI data for the cathodal stimulation site

Transcranial direct current stimulation (tDCS) over prefrontal cortex (PFC) regions is currently proposed as therapeutic intervention for major depression and other psychiatric disorders. The in-depth mechanistic understanding of this bipolar and non-focal stimulation technique is still incomplete. In a pilot study, we investigated the effects of bifrontal stimulation on brain metabolite levels and resting state connectivity under the cathode using multiparametric MRI techniques and computational tDCS modeling. Within a double-blind cross-over design, 20 subjects (12 women, 23.7 ± 2 years) were randomized to active tDCS with standard bifrontal montage with the anode over the left dorsolateral prefrontal cortex (DLPFC) and the cathode over the right DLPFC. Magnetic resonance spectroscopy (MRS) was acquired before, during, and after prefrontal tDCS to quantify glutamate (Glu), Glu + glutamine (Glx) and gamma aminobutyric acid (GABA) concentration in these areas. Resting-state functional connectivity MRI (rsfcMRI) was acquired before and after the stimulation. The individual distribution of tDCS induced electric fields (efields) within the MRS voxel was computationally modelled using SimNIBS 2.0. There were no significant changes of Glu, Glx and GABA levels across conditions but marked differences in the course of Glu levels between female and male participants were observed. Further investigation yielded a significantly stronger Glu reduction after active compared to sham stimulation in female participants, but not in male participants. For rsfcMRI neither significant changes nor correlations with MRS data were observed. Exploratory analyses of the effect of efield intensity distribution on Glu changes showed distinct effects in different efield groups. Our findings are limited by the small sample size, but correspond to previously published results of cathodal tDCS. Future studies should address gender and efield intensity as moderators of tDCS induced effects.

Profiling of bioactive metabolites during the ripening of a semi-hard non-starter culture cheese to detect functional dietary neurotransmitters

Abstract In the present study, the profile of bioactive metabolites in Lighvan cheese, a traditional Iranian semi-hard cheese produced with non-pasteurized ewes' milk and non-starter culture, was investigated during the ripening period to characterize the potential neurotransmitters. Lighvan cheese was prepared according to the local recipe and sampling was done at four stages of ripening (1, 60, 120 and 180 days). The metabolomics was monitored using gas chromatography/mass spectrometry (GC/MS) method and the obtained data were elaborated by principal component analysis (PCA). The results revealed that the content of gamma amino-butyric acid (GABA), glutamate, dopamine, and tyramine known as dietary neurotransmitters were elevated during the ripening process in Lighvan cheese mainly produced by Enterococci and Lactobacilli. Thus, the profile of metabolites of Lighvan cheese exhibited that Lighvan cheese could be a considerable source of dietary neurotransmitters. These compounds may indirectly affect human mood and health through the enteric neuron system.

A meta-analysis of ultra-high field glutamate, glutamine, GABA and glutathione 1HMRS in psychosis: Implications for studies of psychosis risk

Ultra-high field proton magnetic resonance spectroscopy (1HMRS) offers a unique opportunity to measure the concentration of neurometabolites implicated in psychosis (PSY). The extant 7 T 1HMRS literature measuring glutamate-associated neurometabolites in the brain in PSY in vivo is small, but a comprehensive, quantitative summary of these data can offer insight and guidance to this emerging field. This meta-analysis examines proton spectroscopy (1HMRS) measures of glutamate (Glu), glutamine (Gln), glutamate+glutamine (Glx), gamma aminobutyric acid (GABA), and glutathione (GSH) across 255 individuals with PSY (121 first episode) and 293 healthy comparison participants (HC). While all five neurometabolites were lower in PSY as compared to HC, only Glu (Cohen's d = −0.18) and GSH (Cohen's d = −0.21) concentrations were significantly lower in PSY, whereas concentrations of Gln, Glx, and GABA did not significantly differ between groups. Notably, 1HMRS methodological choices and sample demographic characteristics did not impact study-specific effect sizes for PSY-related Glu or GSH differences. This review thus provides further evidence of neurometabolite dysfunction in first episode and chronic PSY, and thereby suggests that Glu and GSH abnormalities may additionally play a role in more incipient stages of the disorder: in clinical high risk stages. Additional 7 T neurochemical imaging studies in larger, longitudinal, and unmedicated samples and in youth at risk for developing psychosis are needed. Such studies will be critical for elucidating the neurodevelopmental and clinical time course of PSY-related neurometabolite alterations, and for assessing the potential for implicated metabolites to serve as druggable targets for decreasing PSY risk.

Increase in Seizure Susceptibility After Repetitive Concussion Results from Oxidative Stress, Parvalbumin-Positive Interneuron Dysfunction and Biphasic Increases in Glutamate/GABA Ratio

Chronic symptoms indicating excess cortical excitability follow mild traumatic brain injury, particularly repetitive mild traumatic brain injury (rmTBI). Yet mechanisms underlying post-traumatic excitation/inhibition (E/I) ratio abnormalities may differ between the early and late post-traumatic phases. We therefore measured seizure threshold and cortical gamma-aminobutyric acid (GABA) and glutamate (Glu) concentrations, 1 and 6weeks after rmTBI in mice. We also analyzed the structure of parvalbumin-positive interneurons (PVIs), their perineuronal nets (PNNs), and their electroencephalography (EEG) signature (gamma frequency band power). For mechanistic insight, we measured cortical oxidative stress, reflected in the reduced/oxidized glutathione (GSH/GSSG) ratio. We found that seizure susceptibility increased both early and late after rmTBI. However, whereas increased Glu dominated the E/I 1week after rmTBI, Glu concentration normalized and the E/I was instead characterized by depressed GABA, reduced per-PVI parvalbumin expression, and reduced gamma EEG power at the 6-week post-rmTBI time point. Oxidative stress was increased early after rmTBI, where transient PNN degradation was noted, and progressed throughout the monitoring period. We conclude that GSH depletion, perhaps triggered by early Glu-mediated excitotoxicity, leads to late post-rmTBI loss of PVI-dependent cortical inhibitory tone. We thus propose dampening of Glu signaling, maintenance of redox state, and preservation of PVI inhibitory capacity as therapeutic targets for post-rmTBI treatment.

Age and Sex Influences Gamma-aminobutyric Acid Concentrations in the Developing Brain of Very Premature Infants

Gamma-aminobutyric acid (GABA) and glutamate are principal neurotransmitters essential for late gestational brain development and may play an important role in prematurity-related brain injury. In vivo investigation of GABA in the preterm infant with standard proton magnetic resonance spectroscopy (1H-MRS) has been limited due to its low concentrations in the developing brain, and overlap in the spectrum by other dominant metabolites. We describe early postnatal profiles of in vivo GABA and glutamate concentrations in the developing preterm brain measured by using the J-difference editing technique, Mescher-Garwood point resolved spectroscopy. We prospectively enrolled very preterm infants born ≤32 weeks gestational age and non-sedated 1H-MRS (echo time 68 ms, relaxation time 2000 ms, 256 signal averages) was acquired on a 3 Tesla magnetic resonance imaging scanner from a right frontal lobe voxel. Concentrations of GABA + (with macromolecules) was measured from the J-difference spectra; whereas glutamate and composite glutamate + glutamine (Glx) were measured from the unedited (OFF) spectra and reported in institutional units. We acquired 42 reliable spectra from 38 preterm infants without structural brain injury [median gestational age at birth of 28.0 (IQR 26.0, 28.9) weeks; 19 males (50%)] at a median postmenstrual age of 38.4 (range 33.4 to 46.4) weeks. With advancing post-menstrual age, the concentrations of glutamate OFF increased significantly, adjusted for co-variates (generalized estimating equation β = 0.22, p = 0.02). Advancing postnatal weeks of life at the time of imaging positively correlated with GABA + (β = 0.06, p = 0.02), glutamate OFF (β = 0.11, p = 0.02) and Glx OFF (β = 0.12, p = 0.04). Male infants had higher GABA + (1.66 ± 0.07 vs. 1.33 ± 0.11, p = 0.01) concentrations compared with female infants. For the first time, we report the early ex-utero developmental profile of in vivo GABA and glutamate stratified by age and sex in the developing brain of very preterm infants. This data may provide novel insights into the pathophysiology of neurodevelopmental disabilities reported in preterm infants even in the absence of structural brain injury.

Analyses of targeted/untargeted metabolites and reactive oxygen species of pepper fruits provide insights into seed browning induced by chilling.

Hot peppers are sensitive to low temperature, and seed browning significantly reduces the fruit quality. This study aims to clarify the mechanisms of seed browning in terms of metabolite changes. Metabolites were analysed during a 30-day-storage period at 2°C and 10°C. Gamma-aminobutyric acid, tyrosine, phenylalanine, and isoleucine concentrations were significantly higher at 2°C storage than at 10°C. Reactive oxygen species (ROS) generation was associated with seed browning. Transcription of jasmonic acid synthesis and ROS scavenging genes were higher in hot peppers stored at 2°C than those stored at 10°C. This study elucidated the mechanisms underlying seed browning and chill damage in hot peppers during storage at low temperatures and our findings may help improve hot peppers' quality following harvesting.

Motor Cortex Function in APOE4 Carriers and Noncarriers.

The ε4 allele of the apolipoprotein-E gene has been associated with disease activity including Alzheimer disease, multiple sclerosis, and cardiovascular disease. Individuals who possess the ε4 variant of this gene (ε4 carriers) also demonstrate higher levels of cognitive impairment and lower motor scores compared with noncarriers. The purpose of this study was to establish whether there is a difference in motor cortex function between apoε4 carriers and noncarriers. We hypothesized that carriers would have lower levels of excitability and excitatory transmitter (glutamate) and similar levels of intracortical inhibition and inhibitory neurotransmitter (gamma-aminobutyric acid) than noncarriers. Fifty-two participants provided saliva samples to determine apoε4 carrier status. Measures of motor cortex excitability and inhibition were obtained using transcranial magnetic stimulation, and measures of glutamate and gamma-aminobutyric acid concentrations were obtained using proton magnetic resonance spectroscopy. No significant differences in transcranial magnetic stimulation (P ≥ 0.19) or proton magnetic resonance spectroscopy measures (P ≥ 0.90) were found between carriers and noncarriers. The results from this study suggest that motor cortex function, as assessed by transcranial magnetic stimulation measures of excitability and inhibition, and MRS measures of excitatory and inhibitory neurotransmitter are similar in those who possess an apoε4 allele and those who do not.

Placental tissue of greenhouse muskmelon (Cucumis melo L.) contains more gamma-aminobutyric acid with antioxidant capacity than the fleshed pulp.

Our previous study revealed that gamma-aminobutyric acid (GABA) in Earl's muskmelon is more concentrated in the inner than the outer parts of the fruit. Here, the GABA and antioxidant capacity of the placental tissue of muskmelon, which is considered waste, were evaluated for possible use as a source of bioactive compounds. The concentrations of GABA and related substances in the placental tissue were significantly higher than in the fleshed pulp, whereas glutamic acid and sugar levels were significantly lower. The two sites showed no difference in GAD activity. Furthermore, the placental site showed high antioxidant capacities based on 2,2-diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity for hydrophilic compounds assays compared with the fleshed pulp, because of the higher levels of total phenolic and L-ascorbic acids. Therefore, the placental tissue of muskmelons may be useful for developing functional foods, which would also reduce the amount of residues during muskmelon processing.

Screening and characterisation of gamma-aminobutyric acid (GABA) producing lactic acid bacteria isolated from Thai fermented fish (Plaa-som) in Nong Khai and its application in Thai fermented vegetables (Som-pak)

This study aimed to evaluate the capability of lactic acid bacteria (LAB) isolated from different kinds of fermented fish products (Plaa-som) on the production of γ-aminobutyric acid (GABA). Among them, isolate L10-11, identified as Lactobacillus plantarum, offered the highest GABA production and was selected for further study. The highest production of GABA was obtained within 48h from the de Man, Rogosa and Sharpe (MRS) medium, having a pH range of 5-6. Increasing the monosodium glutamate (MSG) concentration resulted in a higher accumulation of GABA and reached the highest concentration (15.74 g/L) using 4% (w/v) MSG, while high residual MSG was also observed in accordance with concentration increase. On the other hand, the addition of NaCl in the culture medium by up to 7% (w/v) did not suppress GABA production. Preliminary application of strain L10-11 as starter producing GABA was investigated in Thai fermented vegetables (Som-pak). It was found that GABA formation could be observed increasingly following the concentration of MSG added. GABA content in Som-pak was 5 times higher than that of control when inoculating Lb. plantarum L10-11 and adding MSG at 1% (w/v). In addition, sensory evaluation revealed that addition of this starter culture to Som-pak gave overall acceptability slightly higher than that which allowed fermentation to occur spontaneously. This alternative procedure would be successful for improving the nutritional quality of functional fermented food.

Anti-convulsant effects of cultures bear bile powder in febrile seizure via regulation of neurotransmission and inhibition of neuroinflammation

Ethnopharmacological relevanceNatural bear bile powder (NBBP) has been used to treat seizures for thousands of years, but its application is greatly restricted due to ethical reasons. Cultured bear bile powder (CBBP), which is produced by biotransformation, may be an appropriate substitute for NBBP. However, the anti-convulsant effects of CBBP and its mechanisms remain unclear. Aim of the studyThis study aimed to investigate the anti-convulsant effects and possible mechanisms of CBBP in a febrile seizure (FS) rat model. Materials and methodsFS was induced by placing the rats in a warm water bath (45.5 °C). The incidence rate and latency of FS, and hematoxylin-eosin staining (HE) were conducted for neurological damage. The levels of 4 bile acids and 8 main neurotransmitters in vivo were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The expression of bile acid related transports, neurotransmitter receptors, inflammatory factors, neurotrophic factors and glial fibrillary acidic protein (GFAP) in hippocampal tissues were detected by real-time PCR, western blotting, and immunohistochemistry. ResultsPre-treatments with CBBP and similarly, NBBP, significantly reduced the incidence rate and prolonged the latency of FS. Additionally, CBBP alleviated the histological injury induced by FS in the rat hippocampus tissue. LC-MS/MS analyses revealed that CBBP markedly increased the levels of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), ursodeoxycholic acid (UDCA), and chenodeoxycholic acid (CDCA) in FS rats. Furthermore, the content of gamma-aminobutyric acid (GABA) was up-regulated in rats pre-treated with CBBP whereas GFAP was down-regulated. CBBP also significantly suppressed the expression of interleukin -1β (IL-1β), tumor necrosis factor α (TNF-α), nuclear factor kappa B (NF-κB), and brain-derived neurotrophic factor (BDNF) and its TrkB receptors, and improved the expression of GABA type A receptors (GABAAR) and farnesoid X receptors (FXR). ConclusionsThe present study demonstrated that CBBP had anti-convulsant effects in a FS rat model. CBBP may protect rats against FS, probably by up-regulating FXR, which was activated by increasing brain bile acids, up-regulating GABAergic transmission by inhibiting BDNF-TrkB signaling, and suppressing neuroinflammation by inhibiting the NF-κB pathway.

Lower cortical gamma-aminobutyric acid level contributes to increased connectivity in sensory-motor regions in progressive MS

BackgroundLarge-scale functional abnormalities and decreased synchronization between functionally connected regions within brain networks were reported in progressive multiple sclerosis (P-MS) patients. Low concentration of gamma-aminobutyric acid (GABA) was observed in the sensorimotor cortex (SMC) of these patients and was associated with reduced motor functions of limbs. Yet, the role of GABA in modulating functional connectivity (FC) has not been investigated in MS patients. ObjectivesTo determine the relationship between GABA concentration in the SMC and short-term FC changes within the sensorimotor network (SMN) in P-MS patients. MethodsCombining magnetic resonance spectroscopy (MRS) and resting-state functional MRI (rs-fMRI), we investigated the relationship between baseline GABA concentration in the left SMC and FC within SMN in P-MS patients compared to healthy controls (HCs). Additionally, we assessed the relationship between baseline GABA concentration and FC changes over a 1-year follow-up period in the patients’ group only. ResultsAt baseline, lower GABA levels, and decreased FC levels in regions within the SMN were observed in MS patients compared to healthy controls (HCs). Overtime, an increase in FC was observed in regions within the SMN in the MS group. This increase correlated inversely with motor performance scores. ConclusionsWe postulate that in P-MS patients, lower levels of GABA in the SMC contribute to decreased inhibition, and as a result, to a reactive increase of FC in inter-connected sensorimotor brain regions, thus minimizing clinical worsening.

M146. NEUROCHEMICAL MODULATION OF AUDITORY CORTEX FUNCTIONAL CONNECTIVITY IN PATIENTS WITH AUDITORY VERBAL HALLUCINATIONS

BackgroundAuditory hallucinations have been linked to aberrant functioning of the left superior temporal gyrus (STG) and are associated with impaired cognitive control regulated by areas in the prefrontal cortex. However, the mechanisms behind these dysfunctions are still unclear.MethodsThe current study combined resting state connectivity fMRI with MR spectroscopy (MRS) in a sample of 81 psychosis patients to explore how neurochemical correlates of auditory hallucinations modulate left STG functioning. The analyses were focused on glutamate (Glu) and gamma-aminobutyric acid (GABA), two neurotransmitters with excitatory and inhibitory functions, respectively, since these have previously been implicated in psychosis.ResultsGlu and GABA showed differential relationships with left STG connectivity in patients with and without hallucinations. Specifically, Glu concentration in the anterior cingulate cortex (ACC) was positively related to functional connectivity between the left and right temporal lobe in hallucinating patients only. In contrast, GABA concentration in the ACC was negatively related to connectivity between the left and right temporal lobe in non-hallucinating patients only.DiscussionThese findings support a recently proposed model of interhemispheric temporal lobe miscommunication in auditory hallucinations and indicate prefrontal neurochemical modulation as a potential underlying mechanism. The results can further be integrated with previously suggested excitatory/inhibitory imbalances as neurochemical modulators in AVH.

Effect of processing conditions on bioactive compounds and glycemic index of the selected landrace rice variety in pre-diabetes

Paddy processing can affect glycemic index (GI) and bioactive compounds of rice. Therefore, the effects of processing conditions such as germination, parboiling and polishing on total polyphenols, ferulic acid and gamma-aminobutyric acid (GABA) contents of seven landrace varieties from Thailand were investigated. Subsequently, the best rice variety was chosen to evaluate GI in pre-diabetic subjects. Four different rice forms used were brown rice (BR), parboiled brown rice (PBR), germinated parboiled brown rice (GPBR) and polished rice (PR). Results showed that polishing process strongly reduced all bioactive compounds. In contrast, parboiling the grains slightly increased polyphenol, and germination followed by parboiling significantly increased polyphenol content. Ferulic acid content was found to be similar among BR, PBR and GPBR and the highest GABA content was found in GPBR. Furthermore, Leuang Awn variety exhibited the highest polyphenol (126.70 ± 1.08 mg GAE/100 g), ferulic acid (17.77 ± 0.16 mg/100 g) and GABA content (78.57 ± 1.00 mg/100 g) and was selected for GI study. PBR and GPBR had medium GI values (55.10 ± 5.37 and 60.58 ± 6.48) and PR showed high GI value (83.10 ± 5.10). In conclusion, parboiling and germination had less effects on the bioactive compounds of whole grain rice and produced low-medium GI, which could be beneficial for health promotion.

Thalamic and prefrontal GABA concentrations but not GABAA receptor densities are altered in high-functioning adults with autism spectrum disorder

The gamma aminobutyric acid (GABA) neurotransmission system has been implicated in autism spectrum disorder (ASD). Molecular neuroimaging studies incorporating simultaneous acquisitions of GABA concentrations and GABAA receptor densities can identify objective molecular markers in ASD. We measured both total GABAA receptor densities by using [18F]flumazenil positron emission tomography ([18F]FMZ-PET) and GABA concentrations by using proton magnetic resonance spectroscopy (1H-MRS) in 28 adults with ASD and 29 age-matched typically developing (TD) individuals. Focusing on the bilateral thalami and the left dorsolateral prefrontal cortex (DLPFC) as our regions of interest, we found no differences in GABAA receptor densities between ASD and TD groups. However, 1H-MRS measurements revealed significantly higher GABA/Water (GABA normalized by water signal) in the left DLPFC of individuals with ASD than that of TD controls. Furthermore, a significant gender effect was observed in the thalami, with higher GABA/Water in males than in females. Hypothesizing that thalamic GABA correlates with ASD symptom severity in gender-specific ways, we stratified by diagnosis and investigated the interaction between gender and thalamic GABA/Water in predicting Autism-Spectrum Quotient (AQ) and Ritvo Autism Asperger’s Diagnostic Scale–Revised (RAADS-R) total scores. We found that gender is a significant effect modifier of thalamic GABA/Water’s relationship with AQ and RAADS-R scores for individuals with ASD, but not for TD controls. When we separated the ASD participants by gender, a negative correlation between thalamic GABA/Water and AQ was observed in male ASD participants. Remarkably, in female ASD participants, a positive correlation between thalamic GABA/Water and AQ was found.